1. Field of the Invention
This invention relates to physiological sensors and methods of using the same. More particularly, this invention relates to a guidewire with a chemical sensor and a method of using the guidewire.
2. Description of the Background
Atherosclerosis refers to a thickened area in the wall of an artery which can partially or completely obstruct the vessel. Most instances of myocardial infarction, cardiac arrest, or stroke are caused by rupture, fissure, or ulceration of the atherosclerotic lesion. The rupture, fissure, or ulceration causes a large thrombus to form in the artery, which can completely occlude the flow of blood through the artery, thereby injuring the heart or brain.
Treatment modalities for atherosclerotic coronary artery disease can include percutaneous transluminal interventions (PTI) such as balloon angioplasty. PTI can relieve myocardial ischemia in patients with coronary artery disease by reducing lumen obstruction and improving coronary flow. Recurrent stenosis or restenosis, characterized by the reocclusion of the coronary artery following PTI remains a significant problem, however. Development of restenosis, typically within 6 months after the procedure, results in significant morbidity and mortality or frequently necessitates further interventions such as repeat angioplasty or coronary bypass surgery.
Reactive oxygen species in general, and the molecule nitric oxide (NO) in particular, are key entities in the processes of atherosclerosis and restenosis. In endothelial cells, NO is formed from the metabolism of L-arginine by endothelial NO synthase (Oeamar et al., “Reduced Endothelial Nitric Oxide Synthase Expression and Prosuction in Human Atherosclerosis” Circulation 1998, v. 97, 2494-2498). Under normal hemodynamic conditions, the production of NO inhibits such processes as monocyte adherence and chemotaxosis, platelet adherence and aggregation, and vascular smooth muscle proliferation, all of which are potential causes of atherosclerosis and restenosis. In contrast, reduced NO expression has been associated with increased endothelial adhesiveness for monocytes and increased lesion formation in pathological rabbit models (Niebauer et al., “Local L-Arginine Delivery After Balloon Angioplasty Reduces Monocyte Binding and Induces Apoptosis.” Circulation 1999, v. 100, 1830-1835). Accordingly, NO is as a key entity in the balance of metabolic and biological processes involved in atherogenesis and restenosis.
Because of the small concentrations of NO expected in vivo, a more complete understanding of sample biological environments can be obtained by making measurements of superoxide concentration in addition to or independent of NO measurements. Superoxide is a key molecular entity in determining the balance of NO released by the endothelium. Superoxide free radicals can be released by activated monocytes and can counteract NO, in effect neutralizing the beneficial properties of NO (Hishikawa and Luscher, “Pulsatile Stretch Simulates Superoxide Production in Human Aortic Endothelial Cells” Circulation 1997, v. 96, 3610-3616). The ratio of NO concentration to superoxide concentration can therefore be a more useful measure than either concentration alone.
Percutaneous treatment strategies for conditions such as atherosclerosis and restenosis are almost always performed without the benefit of specific knowledge of the biological environment of the lesion. While the procedures are usually initially successful, six month restenosis rates of 30% or higher are not uncommon post-procedure outcomes. Therefore, the ability to monitor the level of NO and/or superoxide present in the immediate vicinity of a lesion could provide important information necessary for a physician to obtain a clearer understanding of the relative condition of the lesion. For example, low NO and high superoxide concentrations could indicate impaired endothelium. As a result, procedures could be optimized based on individual lesion status.
Detection methods for both NO and superoxide in biological vessels and tissue are presently available. Chemoluminescent NO sensors can employ a NO sensing compound, typically containing iron, manganese, cobalt, platinum, osmium, and/or ruthenium, imbedded in a film or plug which is incorporated into the end of a fiber optic sensor. The optical characteristics of the NO sensing compound when exposed to the vessel or tissue is determinative of the NO concentration.
Other NO sensors employ methods including mass spectrometry, use of high-pressure cadmium columns (by measuring NO by-products), dithionite and hemoglobin treatment, solution methods, and electrical resistance across an electrode having a catalytic material capable of catalyzing oxidation of NO coated with a cationic exchanger. Superoxide detection methods are similar.
Accordingly, it would benefit medical professionals to be able to analyze NO and superoxide levels in vivo, and, if treatment is decided upon at the time of analysis, also begin entry of a treatment catheter with minimal additional time, energy, and medical devices.